This proposal will focus on the role of estrogen receptor (ER) and progesterone receptor (PR) containing neurons in the onset of maternal behavior and the attendent neuroendocrine events in the maternally responsive female rat. Specific Aim I- Does pregnancy alter the brain's sensitivity to steroids by induction of ER and PR in the preoptic area (POA) and limbic system? Are these alterations at the transcriptional or translational level? We will test whether the number and distribution of POA and limbic neurons that contain ER and PR is altered during pregnancy and if the amount of receptor protein or mRNA per neuron is altered. Immunocytochemistry (ICC) with ER and PR antibodies or in situ hybridization (or Northern blot) with probes to ER and PR mRNA will be used. Specific Aim II- Is the brain's sensitivity to estrogen and progestin channeled through particular neural circuits that underlie specific components of maternal responsiveness? Do unique efferent projections of ER and PR neurons underlie the different components of the maternal response including altered responsivity to chemosensory inputs, the motor components related to nest building and retrieval, and events related to nursing including crouching, licking and oxytocin release? These experiments will combine retrograde neuroanatomical tracing with ICC detection of ER and PR. Will lesions of the specific populations of ER and PR POA neurons that project to different functional regions alter specific components of the maternal response? Neurotoxins will be used to lesion specific subsets of preoptic neurons that will be defined by their unique efferent projections and/or pregnancy altered concentration of receptors ; behavioral impairment will be tested. Specific Aim III- ER and PR in neuronal populations important for maternal responsiveness could be induced by a number of the important physiological events that occur during the natural course of pregnancy. These experiments will test whether the afferent input to POA alters the induction of ER and PR in the POA during pregnancy. Tetrodotoxin or neurotransmitter antagonists will be used to transiently eliminate afferent input to these neurons; lesion of the chemosensory input carried out. Immunoreactive receptor protein or mRNA content and behavioral results will be examined.